[1942] Mismatch Repair Protein (MMR) Immunohistochemistry: A 2-Antibody Screening Panel Is Equally Efficacious for Intestinal and Extraintestinal Tumors

A Mojtahed, I Schrijver, JM Ford, TA Longacre, RK Pai. Stanford University Medical Center, Stanford, CA

Background: Mismatch repair (MMR) protein immunohistochemistry (IHC) is a widely used method for detecting patients at risk for hereditary non-polyposis colorectal carcinoma (HNPCC) syndrome. Recent data suggest a 2-antibody panel approach (PMS2 and MSH6) is an effective screening protocol for colorectal carcinoma, but this has not been independently confirmed and there are limited data concerning this approach for extraintestinal tumors.
Design: 281 cases (219 colorectal carcinoma, 34 skin sebaceous tumors, 22 gynecologic carcinomas, and 6 other extraintestinal tumors) were identified for testing based on concern for HNPCC or pathologic features of MSI. IHC was performed for MLH1, MSH2, MSH6, and PMS2. Protein expression loss was defined as absence of tumor nuclear staining with concurrent positive labeling of normal tissue. MSI PCR was performed on colorectal tumor and normal tissue for microsatellite loci BAT-25, BAT-26, MONO-27, NR-21, and NR-24.
Results: The most common abnormality was concurrent loss of MLH1/PMS2 (38/281, 14%) followed by concurrent loss of MSH2/MSH6 (28/281, 10%). Isolated loss of MSH6 was often seen (11/281, 4%); rare cases demonstrated isolated loss of PMS2 (3/281, 1%). Isolated loss of MLH1 or MSH2 was not observed. For colorectal carcinomas, loss of MLH1/PMS2 and loss of MSH2/MSH6 most often resulted in high MSI (25/26, 96% and 9/12, 75%, respectively).

Table 1. Summary of MMR Results

	Colorectal Neoplasms (n=219)	Skin Neoplasms (n=34)	Gynecologic Neoplasms (n=22)
Immunohistochemical Pattern	No. Cases (%)	No. Cases (%)	No. Cases (%)
Loss of MLH1 and PMS2	27 (12%)	6 (18%)	5 (23%)
Loss of MLH1 alone	0 (0%)	0 (0%)	0 (0%)
Loss of PMS2 alone	3 (1%)	0 (0%)	0 (0%)
Loss of MSH2 and MSH6	12 (6%)	13 (38%)	3 (14%)
Loss of MSH2 alone	0 (0%)	0 (0%)	0 (0%)
Loss of MSH6 alone	6 (3%)	2 (6%)	3 (14%)
Loss of at least 1 protein	48 (22%)	21 (62%)	11 (50%)
All proteins tested intact	171 (78%)	13 (38%)	11 (50%)

6 neoplasms from other extraintestinal sites (CNS, ampulla, stomach) showed intact MMR proteins.


Conclusions: Our findings suggest that a 2-antibody MMR panel with PMS2 and MSH6 may be a sufficient initial screening tool for cutaneous (sebaceous), gynecologic, and colorectal carcinomas. The pattern of MMR protein loss by IHC in extraintestinal sites is similar to intestinal (colorectal) sites.
Category: Techniques

Monday, March 22, 2010 8:45 AM

Platform Session: Section G 1, Monday Morning